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TRANSCRIPTIONAL REGULATION

NF-κB and AP-1 Connection: Mechanism of NF-κB-Dependent Regulation of AP-1 Activity

Shuichi Fujioka, Jiangong Niu, Christian Schmidt, Guido M. Sclabas, Bailu Peng, Tadashi Uwagawa, Zhongkui Li, Douglas B. Evans, James L. Abbruzzese, Paul J. Chiao
Shuichi Fujioka
1Department of Surgical Oncology
2Department of Molecular and Cellular Oncology
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Jiangong Niu
1Department of Surgical Oncology
3The Program in Cancer Biology, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas
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Christian Schmidt
1Department of Surgical Oncology
2Department of Molecular and Cellular Oncology
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Guido M. Sclabas
1Department of Surgical Oncology
4Department of Visceral and Transplantation Surgery, Inselspital, University of Bern, Bern, Switzerland
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Bailu Peng
1Department of Surgical Oncology
2Department of Molecular and Cellular Oncology
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Tadashi Uwagawa
1Department of Surgical Oncology
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Zhongkui Li
1Department of Surgical Oncology
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Douglas B. Evans
1Department of Surgical Oncology
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James L. Abbruzzese
5Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center
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Paul J. Chiao
1Department of Surgical Oncology
2Department of Molecular and Cellular Oncology
3The Program in Cancer Biology, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas
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  • For correspondence: pjchiao@mdanderson.org
DOI: 10.1128/MCB.24.17.7806-7819.2004
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ABSTRACT

Nuclear factor κB (NF-κB) and activator protein 1 (AP-1) transcription factors regulate many important biological and pathological processes. Activation of NF-κB is regulated by the inducible phosphorylation of NF-κB inhibitor IκB by IκB kinase. In contrast, Fos, a key component of AP-1, is primarily transcriptionally regulated by serum responsive factors (SRFs) and ternary complex factors (TCFs). Despite these different regulatory mechanisms, there is an intriguing possibility that NF-κB and AP-1 may modulate each other, thus expanding the scope of these two rapidly inducible transcription factors. To determine whether NF-κB activity is involved in the regulation of fos expression in response to various stimuli, we analyzed activity of AP-1 and expression of fos, fosB, fra-1, fra-2, jun, junB, and junD, as well as AP-1 downstream target gene VEGF, using MDAPanc-28 and MDAPanc-28/IκBαM pancreatic tumor cells and wild-type, IKK1−/−, and IKK2−/− murine embryonic fibroblast cells. Our results show that elk-1, a member of TCFs, is one of the NF-κB downstream target genes. Inhibition of NF-κB activity greatly decreased expression of elk-1. Consequently, the reduced level of activated Elk-1 protein by extracellular signal-regulated kinase impeded constitutive, serum-, and superoxide-inducible c-fos expression. Thus, our study revealed a distinct and essential role of NF-κB in participating in the regulation of elk-1, c-fos, and VEGF expression.

  • Copyright © 2004 American Society for Microbiology
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NF-κB and AP-1 Connection: Mechanism of NF-κB-Dependent Regulation of AP-1 Activity
Shuichi Fujioka, Jiangong Niu, Christian Schmidt, Guido M. Sclabas, Bailu Peng, Tadashi Uwagawa, Zhongkui Li, Douglas B. Evans, James L. Abbruzzese, Paul J. Chiao
Molecular and Cellular Biology Aug 2004, 24 (17) 7806-7819; DOI: 10.1128/MCB.24.17.7806-7819.2004

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NF-κB and AP-1 Connection: Mechanism of NF-κB-Dependent Regulation of AP-1 Activity
Shuichi Fujioka, Jiangong Niu, Christian Schmidt, Guido M. Sclabas, Bailu Peng, Tadashi Uwagawa, Zhongkui Li, Douglas B. Evans, James L. Abbruzzese, Paul J. Chiao
Molecular and Cellular Biology Aug 2004, 24 (17) 7806-7819; DOI: 10.1128/MCB.24.17.7806-7819.2004
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KEYWORDS

Gene Expression Regulation
NF-kappa B
signal transduction
Transcription Factor AP-1

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